Many pathological conditions such as preeclampsia, peripheral vascular disease, erectile dysfunction, cancers, renal failure, heart disease, and stroke are often associated with alterations in the normal vascular condition of the affected tissues and/or systems. While the change from normal vascular condition may arise through natural physiological processes, it may also be induced transiently by perturbations such as surgical procedures, and by the presence of exogenous agents within the body. The change in vascular condition can result in a reduction in blood flow to the associated organ or system, rendering that organ or system hypoxic.
This invention relates to methods for diagnosing vascular conditions, and to methods for detecting hypoxia or endothelial dysfunction in an individual. In one aspect, the invention relates to a method for diagnosing a vascular condition leading to a hypoxic state. The methods of the invention comprise the steps of:
i) measuring the level of at least one substance in at least one biological sample, said substance having a level which is affected by a vascular condition associated with a reduction in blood flow, hypoxia or endothelial dysfunction; and
ii) comparing the level of the substance in said biological sample with a standard to determine the extent of said vascular condition associated with a reduction in blood flow, hypoxia or endothelial dysfunction.
According to a further aspect of the method of the invention, a corresponding measure of the level of at least one substance is performed in at least one different biological sample, said different biological sample being unaffected by a vascular condition associated with a reduction in blood flow, hypoxia or endothelial dysfunction. The substance may be selected from the group consisting of genes, gene products, metabolites, metabolic by-products, hormones, and exogenous agents.
In a particular embodiment, the invention is a method of diagnosing a vascular condition associated with a reduction in the flow of blood within an anatomical site of an individual and the substance measured is a product of the RTP/Drg1 gene.
In additional embodiments, the invention is a method of detecting hypoxia or endothelial dysfunction in an individual and the substance measured is a product of a gene selected from the group consisting of RTP/Drg1, uPAR and PAI-1. In another embodiment, the invention is a method of detecting hypoxia or endothelial dysfunction in an individual and the substance measured is an arginine metabolite, such as L-NMMA or ADMA.
In another embodiment, the invention is a method of diagnosing a vascular condition in an individual, comprising the steps of:
i) measuring the quantity of at least two substances chosen from the group consisting of a product of the RTP/Grp1 gene, a product of the uPAR gene, a product of the PAI-1 gene and an arginine metabolite, in at least one biological sample obtained from said individual; and
ii) comparing the measured quantity of said substances to a standard value for the quantity of said substances in a normal biological sample; wherein
an increase in the measured quantity of at least one of said substances relative to the standard value is indicative of said vascular condition. The method of this embodiment can further comprise an indirect assay, such as evaluating the in vitro invasiveness of cells isolated from said individual.
In a further embodiment, the invention is a method of assessing an individual""s risk for a vascular condition associated with a reduction in the flow of blood, comprising
i) measuring the quantity of a product of the RTP/Drg1 gene in at least one biological sample; and
ii) comparing the quantity of said product of the RTP/Drg1 gene in said biological sample with a standard; wherein
an increase in the measured quantity of said RTP/Drg1 gene product relative to the standard value is indicative of risk for said vascular condition, and said risk correlates with the degree to which said RTP/Drg1 gene product is elevated.
The invention also relates to a method of diagnosing a vascular condition in an individual. The method comprises detecting at least one endocrine disrupter in at least one biological sample obtained from an individual, wherein the presence of said endocrine disrupter is indicative of said vascular condition. In one embodiment, the endocrine disrupter p,p-DDE is detected to diagnose erectile dysfunction.